Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, 2019 Olivet Nazarene University
Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte
Honors Program Projects
Hexavalent chromium, or Cr(VI), is a potent oxidizer and known carcinogen, that is found at varying levels in the water sources of more than 200 million Americans. However, the exact mechanism of carcinogenicity remains unknown, and though the government currently regulates total chromium levels, they have yet to determine a permissible exposure limit for Cr(VI). Moreover, there is currently no preventative treatment for Cr(VI). Because of Cr(VI)’s strong oxidative power, we hypothesized that it causes DNA mutation and cell death via oxidation and that antioxidants could prevent this from occurring. To test this, we first ...
Barriers And Facilitators To Genetic Testing For Familial Hypercholesterolemia In The United States: A Review, 2019 Harvard Medical School
Barriers And Facilitators To Genetic Testing For Familial Hypercholesterolemia In The United States: A Review, Rachele M. Hendricks-Sturrup, Kathleen M. Mazor, Amy C. Sturm, Christine Y. Lu
Open Access Articles
Familial Hypercholesterolemia (FH) is an underdiagnosed condition in the United States (US) and globally, affecting an estimated 1/250 individuals. It is a genetic risk factor for premature cardiovascular disease and is responsible for an estimated 600,000 to 1.2 million preventable vascular events. Studies show that FH genetic testing can identify a causal gene variant in 60 to 80% of clinically suspected FH cases. However, FH genetic testing is currently underutilized in clinical settings in the US despite clinical recommendations and evidence supporting its use. Reasons for underutilization are not well understood. We conducted a literature review in ...
F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, 2019 Savitribai Phule Pune University
F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra
Open Access Articles
Aberrant activation of beta-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/beta-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear beta-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of beta-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of beta-catenin. Therefore, depletion ...
A Case Report Of Water Hemlock Poisoning, 2019 Maine Medical Center
A Case Report Of Water Hemlock Poisoning, Blue Butterfield, Alicia Bond Md, Dan Meyer, Gary Diperna, Tamas Peredy Md
Journal of Maine Medical Center
Introduction: Water hemlock poisoning is an uncommon cause of seizures, gastrointestinal upset, and renal failure. This poisoning occurs infrequency and is likely to go unrecognized without a proper history and consideration in the differential diagnosis.
Clinical Findings: A 23-year-old male with an unremarkable past medical history presented to the emergency department after being found unresponsive at a farm where he was employed. He had several tonic-clonic seizures en route. Initial evaluation was unremarkable and included toxicology screening, lumbar puncture, and brain imaging.
Main diagnoses, therapeutics, interventions, and outcomes: The patient was treated with broad-spectrum antibiotics and antivirals with a suspected ...
Incivility Among Radiography Educators In The United States, 2019 The University of Texas MD Anderson Cancer Center
Incivility Among Radiography Educators In The United States, Kevin R. Clark, Jessyca B. Wagner
Internet Journal of Allied Health Sciences and Practice
Purpose: Medical imaging education must nurture a civil environment for both students and educators. Because faculty incivility can potentially compromise learning and interfere with workplace productivity, this study examined the perceptions of incivility among radiography educators in the United States.
Methods: A survey research method was designed to examine the severity and frequency of incivility among educators teaching in radiography programs accredited by the Joint Review Committee on Education in Radiologic Technology (JCERT). Using a scale of 1 to 4, the participants in this study considered their perceptions of faculty incivility among radiography educators within their respective departments.
Results: Civility ...
Phylogenetic Estimates Of Hiv-1 Gp120 Indel Rates Across The Group M Subtypes, 2019 Western University
Phylogenetic Estimates Of Hiv-1 Gp120 Indel Rates Across The Group M Subtypes, John Palmer, Art Poon
Western Research Forum
Insertions and deletions (indels) in the HIV-1 envelope glycoprotein gp120 play a significant role in the evolution of HIV pathogenesis and transmission fitness. While substitution rates in HIV-1 are well characterized by phylogenetic models, there is a lack of quantitative measures of indel rates in HIV-1. Here we use a dated-tip phylogenetic analysis of gp120 sequences to estimate indel rates for 7 subtypes and CRFs of HIV-1 group M.
We obtained and processed 26,359 HIV-1 gp120 sequences from the Los Alamos National Laboratory HIV Sequence database. After filtering these sequences, we extracted the conserved and variable regions from the ...
Mouse Performance On A Novel Touchscreen Continuous Performance Task Is Dependent On Signaling In The Prelimbic Cortex, Tyler D. Dexter, Daniel Palmer, Amy C. Reichelt, Anita Taksokhan, Lisa M. Saksida, Tim J. Bussey
Western Research Forum
Attention is the cognitive processing that facilitates the ability to target and attend to relevant environmental stimuli, while filtering out irrelevant or distracting stimuli. Control over selective attention is theorized to be dependent on organized neural communication that stems from the medial prefrontal cortex (mPFC). To evaluate selective and sustained attention, mice were trained on the novel touchscreen rodent continuous performance task (rCPT), a task designed to emulate the human CPT. In the rodent version, images are continuously presented on a touchscreen, where mice have been trained to selectively respond to one image type while suppressing responses to all others ...
Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, 2019 The University of Western Ontario
Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang
Western Research Forum
Transplantation is invariably associated with acute allograft injury caused by ischemia reperfusion injury (IRI). This injury causes cells of the allograft to undergo various forms of programmed cell death including apoptosis and necroptosis. During programmed cell death, immunogenic molecules are released from cells, one of which is cell-free DNA (cfDNA). We hypothesize that cfDNA is released by microvascular endothelial cells (MVECs) during programmed cell death of IRI and that cfDNA acts as both a biomarker for cellular injury as well as a biologically active molecule capable of amplifying inflammation and organ injury.
Our results indicate that cfDNA is released by ...
Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, 2019 University of Michigan - Ann Arbor
Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, Brock Humphries, Zhishan Wang, Chengfeng Yang
Toxicology and Cancer Biology Faculty Publications
Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs ...
Dysfunctional Stem And Progenitor Cells Impair Fracture Healing With Age, 2019 Marian University - Indianapolis
Dysfunctional Stem And Progenitor Cells Impair Fracture Healing With Age, Dr Wagner, S Karnik, Zj Gunderson, Jj Nielsen, A Fennimore, Hj Promer, Jonathan W. Lowery Ph.D., Mt Loghmani, Ps Low, To Mckinley, Ma Kacena, M Clauss, J Li
Faculty Publications and Research
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with ...
M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, 2019 University of Chicago
M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He
Department of Cancer Biology Faculty Papers
Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of ...
Behavioral Responses To Gold Nanoparticle Exposure And H2o2-Induced Oxidative Stress In Caenorhabditis Elegans, Rachel Pride, Ashley Wagner
Gold nanoparticles (AuNPs) have been utilized in many biomedical disciplines, most notably cancer therapy and drug delivery. Recent research suggests that with specific peptide manipulation, AuNPs can deliver drugs across the blood-brain barrier (BBB), allowing for treatment of neurodegeneration and other neurological afflictions. Neurodegeneration has been shown to be caused by oxidative stress. The present experiment aimed to assess the effects of AuNPs on C. elegans behavior that had undergone H2O2-induced oxidative stress. It was predicted that worms exposed to both H2O2 and AuNPs would have higher survival, mechanosensation, and thrashing rates than ...
Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, 2019 Goethe University
Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi
Pharmacy Faculty Articles and Research
Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of ...
Identification Of Small Molecule Enzyme Inhibitors As Broad-Spectrum Anthelmintics, 2019 Washington University in St. Louis
Identification Of Small Molecule Enzyme Inhibitors As Broad-Spectrum Anthelmintics, Rahul Tyagi, Elfawal A. Mostafa, Scott A. Wildman, Jon Helander, Christina A. Bulman, Judy Sakanari, Bruce A. Rosa, Paul J. Brindley, James W. Janetka, Raffi V. Aroian, Makedonka Mitreva
Open Access Articles
Targeting chokepoint enzymes in metabolic pathways has led to new drugs for cancers, autoimmune disorders and infectious diseases. This is also a cornerstone approach for discovery and development of anthelmintics against nematode and flatworm parasites. Here, we performed omics-driven knowledge-based identification of chokepoint enzymes as anthelmintic targets. We prioritized 10 of 186 phylogenetically conserved chokepoint enzymes and undertook a target class repurposing approach to test and identify new small molecules with broad spectrum anthelmintic activity. First, we identified and tested 94 commercially available compounds using an in vitro phenotypic assay, and discovered 11 hits that inhibited nematode motility. Based on ...
Exercise To Combat Neurocognitive Decline In Older Adults, 2019 Western University
Exercise To Combat Neurocognitive Decline In Older Adults, Joyla Furlano
Western Research Forum
Background: Older adults with type 2 diabetes (T2D) experience cognitive decline and neural atrophy, and therefore are at high risk for developing dementia. Consequently, older adults at-risk for developing T2D (i.e., overweight or pre-diabetic individuals) are at higher risk for cognitive decline, and intervening at this point may prevent or delay the onset of such decline. One promising lifestyle intervention that may improve neurocognitive function is exercise. For example, 6 months of aerobic training improves cognitive function in overweight or pre-diabetic older adults, but research has not examined whether resistance training (RT) can produce comparable results in this population ...
Adaptive Evolution Targets A Pirna Precursor Transcription Network, 2019 University of Massachusetts Medical School
Adaptive Evolution Targets A Pirna Precursor Transcription Network, Swapnil S. Parhad, Tianxiong Yu, Gen Zhang, Nicholas P. Rice, Zhiping Weng, William E. Theurkauf
University of Massachusetts Medical School Faculty Publications
In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but the cuff gene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show that Drosophila simulans cuff is a dominant negative allele when expressed in Drosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP ...
A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, 2019 University of Massachusetts Medical School
A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, Kristin Abramo, Anne-Laure Valton, Sergey V. Venev, Hakan Ozadam, A. Nicole Fox, Job Dekker
University of Massachusetts Medical School Faculty Publications
Chromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient ...
Characterization Of A Non-Contact Imaging Scintillator-Based Dosimetry System For Total Skin Electron Therapy., Irwin I. Tendler, Petr Bruza, Michael Jermyn, Xu Cao, Benjamin B. Williams, Lesley A. Jarvis, Brian W. Pogue, David J. Gladstone
Open Dartmouth: Faculty Open Access Scholarship
Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick × 15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied ...
Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., 2019 Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, PA 19107, United States; Institute of Biomembranes and Bioenergetics, National Research Council, Via Amendola 165/A, Bari, 70126, Italy
Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet
Department of Biochemistry and Molecular Biology Faculty Papers
Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion ...
Lipoprotein(A) Plasma Levels, Bone Mineral Density And Risk Of Hip Fracture: A Post Hoc Analysis Of The Women's Health Initiative, Usa, Bernhard Haring, Carolyn J. Crandall, Laura Carbone, Simin Liu, Wenjun Li, Karen C. Johnson, Jean Wactawski-Wende, Aladdin H. Shadyab, Margery L. Gass, Victor Kamensky, Jane A. Cauley, Sylvia Wassertheil-Smoller
OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women.
DESIGN: Post hoc analysis of data from the Women's Health Initiative (WHI), USA.
SETTING: 40 clinical centres in the USA.
PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast ...